title: Critical evaluation of the combined model approach for estimation of prehepatic insulin secretion.
abstract: The combined model approach uses kinetic analysis of both plasma insulin and C-peptide dynamics to estimate prehepatic insulin secretion rates and parameters of insulin and C-peptide kinetics. The original model used single-compartment kinetics to describe both insulin and C-peptide despite knowledge that C-peptide follows two-compartment kinetics. The performance of the model under rapidly changing secretory conditions has come into question. Thus a more complex combined model is introduced, incorporating two-compartmental C-peptide disappearance. The addition of two-compartment C-peptide kinetics required a novel numerical approach to allow estimation of model parameters. This simulation study was undertaken to 1) compare the performance of the original combined model and 2) examine the numerical method used to identify parameters for the extended combined model with two-compartment C-peptide kinetics under simulated conditions of rapidly changing insulin and C-peptide. Monte Carlo simulation revealed that the original combined model does not provide accurate estimates of prehepatic insulin secretion under rapid kinetics. However, the extended combined model provides accurate reconstruction of prehepatic insulin secretory profile without separate quantification of C-peptide kinetics.
authors.affiliation: Department of Exercise Science, University of Southern California, Los Angeles 90082-0652, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Watanabe
authors.forename: G M
authors.initials: GM
authors.lastname: Steil
authors.forename: R N
authors.initials: RN
authors.lastname: Bergman
mesh_terms: D000818:Animals; D002096:C-Peptide / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D007700:Kinetics; D016018:Least-Squares Analysis; D008099:Liver / Q000502:physiology*; D008433:Mathematics; D008954:Models, Biological; D009010:Monte Carlo Method
chemical_list: D002096:C-Peptide; D007328:Insulin